The cytoplasmic site of gene expression and use of virally encoded enzymes is a distinguishing feature of vaccinia virus and other poxvirus vector systems that probably accounts for their consistent ability to express foreign genes derived from a variety of prokaryotic, eukaryotic, and viral sources. This feature, together with their ability to stably integrate and package large amounts of DNA without loss of infectivity, their wide host range, and the development of simple and effective methods for isolating recombinant viruses account for their diverse use and popularity. During the past year, emphasis has been placed on the evaluation of the highly attenuated MVA strain of vaccinia virus as an expression vector. Because of the inability of MVA to replicate in human cells, it provides excellent safety. Following the demonstration of high levels of expression of a reporter gene in nonpermissive human cells, a series of transfer vectors was produced to allow vaccine testing in experimental animals. These tests indicate that recombinant MVA vectors provoke good immune responses and disease protection.